Project Summary/Abstract Multiple myeloma is the second most common hematologic malignancy in the US, with about 25,000 new cases in the US each year. Most patients with MM relapse and eventually become unresponsive to treatment. Although multiple new therapies for MM have come on the market, their promise is limited by concerns about toxicity and low efficacy, and MM remains incurable. Therefore, there is an urgent, demonstrable, and sizeable need for safe and efficacious therapies for MM. By significantly augmenting the efficacy of mAb therapies, our new immuno oncology product will capture a significant share of the market for MM-specific mAbs. The proposed project will therefore advance the science of MM-focused immunotherapy while meeting an important need in a rapidly growing market. Indapta Therapeutics, Inc. (`Indapta') has entered into a relationship with the University of California, San Francisco (UCSF) to develop and test a next-generation cancer therapy. Indapta aims to become a leader in safe and effective cellular immuno-oncology therapy by building on a novel discovery by professors from UCSF, Michigan State University and Stanford University confirming a unique synergy between monoclonal antibodies (mAbs) and a specific and potent variety of `natural killer' (NK) immune cell lacking the Fc?RI? adapter (the g-NK cell). The scientific premise is that the conventional NK cells that have mutated after coming into contact with CMV to be lacking the Fc?RI? adapter (G-NK) will significantly increase ADCC and favorable apoptosis in the presence of a MAB to increase tumor killing. The product will combine these special g-NK cells with a targeting mAb, daratumumab to destroy multiple myeloma (MM) cells with high precision and efficacy. Indapta owns the exclusive license to the patents protecting this technology. The PI for this grant is Dr. Vaughn Smider, PhD in Immunology from Stanford and immune oncology professor at Scripps, who has commercialized seveal leading monoclonal antibodies. CEO of Indapta has secured two NCI SBIR Fast-Track grants totaling $4.6M for his first company, which has attracted over $93M in venture funding as it moves to commercialize its early-stage technology. The UCSF team includes a leader in clinical NK cell therapy for MM and a translational scientist with extensive expertise in preclinical models of MM. Indapta's product, pairs g-NK cells with daratumumab to target MM cells. This pairing enables NCT to (i) harness the high potency of g-NK cells, (ii) identify MM cells by using a specialized mAb, daratumumab, (iii) lower the risk of adverse immune response, a feature of genetically engineered immunotherapies, because g-NK cells occur naturally, and (iv) benefit from the longevity (4-9 months) of g-NK cells as compared to conventional NK cells (~2 weeks), thereby reducing frequency of infusions as part of the immunologic regimen.